The case-control follow-up (CCFU) study is a hybrid design, a combination of case control and cohort or follow-up studies. In such studies, a cohort is monitored for early or sentinels events, which are closely associated with some outcome of interest (e.g., diagnosis of breast cancer); information is obtained on all subjects developing the sentinel events, and on a sample of the remaining subjects. Subjects developing the sentinel event (and sometimes other subjects) are then followed prospectively for an event of interest (e.g., death from breast cancer). The design has been employed in studies of the efficacy of cancer screening and of spontaneous abortion but has generally been mistaken for a case-control design. The purpose of this project is to advance understanding of the design and improve inference derived from it. This will be done by 1) developing a general notation and theory for describing these studies; 2) applying and developing appropriate statistical methods for analyzing data arising from these studies; and 3) comparing various approaches for analyzing these studies. We have identified two main general statistical approaches for these studies: one we term the direct approach and the other we call the synthetic approach. We propose to elaborate these approaches, and then consider how to deal with biases that may arise in each of them. New and familiar methods will be assessed through simulation, through application to several CCFU studies, and through artificial generation of CCFU studies by sampling from cohort studies.